Study in Healthy Male Subjects to Demonstrate Bioequivalence of 1600 μg Selexipag Administered as Eight Tablets of 200 μg or as Single Tablet of 1600 μg

Actelion Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Bioequivalence

Treatments: Drug: selexipag

Study type: Interventional

Funder types: Industry

Identifiers

NCT02206295

AC-065-108

Details and patient eligibility

About

The primary aim of this study is to demonstrate bioequivalence in the rate and extent of absorption between 1600 μg selexipag test drug (administered orally as film-coated tablets of 1600 μg, twice a day (b.i.d.) and 1600 μg selexipag reference drug (administered orally as 8 film-coated tablets of 200 μg b.i.d.) at steady-state in healthy male subjects following a multiple-dose up-titration scheme.

Enrollment: 80 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Signed informed consent in the local language prior to any study-mandated procedure.
• Healthy male subjects aged between 18 and 55 years (inclusive) at Screening.
• No clinically significant findings on the physical examination at Screening.
• Body mass index of 18.0 to 30.0 kg/m^2 (inclusive) at Screening.
• Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 beats per minute (all inclusive), measured at Screening.
• 12-lead electrocardiogram without clinically relevant abnormalities, measured at Screening.
• Hematology, clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent at Screening.
• Negative results from urine drug screen and alcohol breath test at Screening.
• Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.

Exclusion criteria

• Known allergic reactions or hypersensitivity to selexipag or any excipient of the drug formulation used in this study.
• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion of selexipag.
• Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
• Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access or puncture; veins with a tendency to rupture during or after puncture).
• Treatment with selexipag or another investigational drug within 1 month prior to Screening or 5 half-lives, whichever is longer.
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to Screening.
• Excessive caffeine consumption at Screening.
• Smoking within 3 months prior to Screening and inability to refrain from smoking during the course of the study.
• Previous treatment with any prescribed medications (including vaccines) or over-the-counter medications within 2 weeks prior to first study drug administration.
• Loss of 500 mL or more of blood within 3 months prior to Screening.
• Positive results from the hepatitis serology (hepatitis B antigen and hepatitis C antibodies), except for vaccinated subjects or subjects with past but resolved hepatitis, at Screening.
• Positive results from the human immunodeficiency virus serology at Screening.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
• Legal incapacity or limited legal capacity at Screening.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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80 participants in 2 patient groups

Treatment Sequence AB

Experimental group

Description:

Subjects will receive Treatment A in Period 1 followed by Treatment B in Period 2. There will be a washout period lasting at least 6 days between treatments. Treatment A: up-titration from Day 1-18 will performed in 200 μg steps every fourth day with multiples of 200 μg film-coated tablets starting with 400 μg selexipag b.i.d. The up-titration will be followed by treatment with 8 film-coated tablets, 200 μg each, b.i.d. from Day 19 to the morning dose of Day 23. Treatment B: up-titration from Day 1-18 will be performed in 200 μg steps every fourth day with multiples of 200 μg film-coated tablets starting with 400 μg selexipag b.i.d. The up-titration will be followed by treatment with one single film-coated tablet, 1600 μg, b.i.d. from Day 19 to the morning dose of Day 23.

Treatment:

Drug: selexipag

Treatment Sequence BA

Experimental group

Description:

Subjects will receive Treatment B in Period 1 followed by Treatment A in Period 2. There will be a washout period lasting at least 6 days between treatments. Treatment A: up-titration from Day 1-18 will performed in 200 μg steps every fourth day with multiples of 200 μg film-coated tablets starting with 400 μg selexipag b.i.d. The up-titration will be followed by treatment with 8 film-coated tablets, 200 μg each, b.i.d. from Day 19 to the morning dose of Day 23. Treatment B: up-titration from Day 1-18 will be performed in 200 μg steps every fourth day with multiples of 200 μg film-coated tablets starting with 400 μg selexipag b.i.d. The up-titration will be followed by treatment with one single film-coated tablet, 1600 μg, b.i.d. from Day 19 to the morning dose of Day 23.

Treatment:

Drug: selexipag